Clinical Chemistry
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Clinical Chemistry 47: 805-806, 2001;
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(Clinical Chemistry. 2001;47:805-806.)
© 2001 American Association for Clinical Chemistry, Inc.

Editorial

Prodrug Metabolites: Implications for Therapeutic Drug Monitoring

Michael Oellericha1 and Victor W. Armstrong1

1 Department of Clinical Chemistry, Georg-August University, Robert-Koch-Strasse 40, D-37075 Göttingen, Germany

aAuthor for correspondence. Fax 49-551-398551; e-mail moeller@med.uni-goettingen.de.

Prodrugs are analogs of active drugs that have been developed to improve the bioavailability and/or tolerability of the latter. Fosphenytoin (1) and mycophenolate mofetil (MMF) (2) are two examples of prodrugs where monitoring of the active drug, the anticonvulsant phenytoin and the immunosuppressant mycophenolic acid (MPA), respectively, is used to guide therapy. The successful application of therapeutic drug monitoring to prodrugs requires a reliable analytical methodology, which in general should be specific for the active drug and should provide timely results so that the clinician can, if necessary, institute appropriate dosage adjustments. Although HPLC-based methodology is the most specific procedure for drug measurements, immunoassays are more rapid; they may, however, be subject to interference through cross-reactivity with structurally related compounds (e.g., prodrugs and drug metabolites). This problem often is aggravated in patients with liver dysfunction or renal insufficiency because of extensive accumulation of drug metabolites.

The use of prodrugs has the following implications for therapeutic drug monitoring:

In this issue of Clinical Chemistry, Annesley et al. (3) report on the isolation and characterization of a novel oxymethylglucuronide metabolite of fosphenytoin, a prodrug of phenytoin. This metabolite has been identified in the plasma of uremic patients . . . [Full Text of this Article]


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